We plan to study the biology of class I genes encoded by the major histocompatibility complex (MHC) of the inbred Balb/c mouse. We have previously cloned and mapped 36 class I genes falling into two categories-three classical transplantation genes which encode the restriction elements for cytotoxic T cells and 33 class I-like genes whose functions are unknown. We plan three major categories of experiments. (1) To express a foreign transplantation antigen (alloantigens) in nonimmunological tissues (pancreas and liver) and in selected iummune-related cells (B cell, T cell and macrophage-like cells). These studies should provide insights into mechanisms of immunological tolerance and H-2 restriction. (2) To secrete and purify large quantities of soluble transplantation antigens in order to crystallize these proteins and determine their three-dimensional structures by X-ray analysis. We will examine in this regard a series of Kb mutant molecules and eventually a transplantation antigen interacting with a peptide fragment. These studies should provide insights into the molecular interactions between H-2 molecules, T-cell receptors and antigen. (3) We have DNA probes specific for most of the class I genes. We plan to study the expression of the 36 class I genes in immunological tissues and cells, in selected nonimmunological tissues and in differentiating T and B cells and in activated T cells. These studies should provide useful lineage and differentiation markers for immune-related cell lines and may provide insights into the function of the class I-like molecules.